Hemostatic function may be severely compromised in patients with renal disease. It is my hypothesis that the bleeding disorders of uremic patients are the result of platelet dysfunction, particularly with regard to reactions involving platelet glycoprotein Ib (GPIb). It has long been accepted that GPIb is a primary site for the binding to platelets of von Willebrand Factor (vWF) and we have recently established that GPIb is the receptor for platelet activation by thrombin. In order to test this hypothesis, studies will be conducted to: 1) Determine the structural integrity of GPIb on platelets from uremic patients with regard to electrophoretic mobility and fragmentation by the platelet Ca++-dependent protease and leukocyte elastase. These studies will determine whether there are primary structural abnormalities in GPIb in uremic platelets due to the effects of proteases or glycosidases known to be present in uremic plasma or of low molecular weight molecules that may bind covalently to GPIb. 2) Study the ability of uremic plasma components to induce similar defects in normal platelets, particularly with regard to the binding of and activation by thrombin and vWF. 3) If these processes have been compromised in uremic platelets, experiments will be conducted to identify the uremic plasma protease, glycosidase or other components which cause these alterations. 4) Study the interaction of thrombin with uremic platelets to ascertain whether their reduced hemostatic effectiveness is a result of a defect in binding to GPIb itself or a defect distal to the receptor in the excitation of the platelet response. The ability of thrombin to bind to uremic platelets and to elicit platelet activation will be measured by aggregation, serotonin release and expression of fibrinogen receptors in comparison to normal platelets. 5) Study the interaction of normal vWF with uremic platelets and determine the structural and functional integrity of uremic vWF. Thus, the capacity of uremic platelets to respond to vWF as well as the ability of uremic vWF to induce a response in normal platelets will be ascertained. The possible synergistic effect of combined defects in the uremic GPIb and uremic vWF will be examined.